Poor-Prognosis Germ Cell Tumours

Abstract

In the International Germ Cell Cancer Consensus Group (IGCCCG) classification, a poor-risk group is defined as either having a mediastinal primary NSGCT, extra-pulmonary visceral metastases or very high serum tumour marker levels (hCG > 50,000 UI/L, AFP > 10,000 ng/mL and/or LDH > 10 times the upper limit value). This subgroup of 10% patients is responsible for most of the deaths from GCT. Their progression-free survival rate is 41 % with only half of them achieving long-term overall survival. Four cycles of the BEP regimen (cisplatin, etoposide and bleomycin), followed by resection of residual masses, became standard treatment for this group in 1987. After a period of 25 years during which all attempts to improve the results of BEP failed, the paradigm changed in 2014 with the use of personalized chemotherapy based on tumour marker decline. That a slow decline in hCG and AFP after the first cycle of BEP chemotherapy can single out patients likely to fail conventional therapy was demonstrated retrospectively and then confirmed prospectively. In the international GETUG-13 trial, once patients had received one cycle of BEP, patients with a favourable tumour marker decline continued BEP and patients with an unfavourable decline were randomised to receive either BEP or a 6-drug dose-dense regimen, including the BEP regimen drugs plus paclitaxel, oxaliplatin, and ifosfamide, with G-CSF support. The primary endpoint of progression-free survival in patients with an unfavourable tumour marker decline receiving dose-dense chemotherapy was improved: 59 % [95 % confidence interval (CI): 49–68] versus 48 % [95 % CI: 38–59] (p = 0.05; HR: 0.66 [0.44–1.00]).The overall probability of curing patients with poor-risk NSGCT managed according to this algorithm (BEP for patients with a favourable decline and dose-dense chemotherapy for patients with an unfavourable decline) now exceeds 75 %. Finally, more and more data support the need to centralise the care of patients with poor-risk NSGCT, and some countries have already implemented this policy at national level.